Stroke
Conditions
Keywords
acute ischemic stroke, LDL-Cholersterol lowering, Endovascular Therapy, PCSK9, clinical trials
Brief summary
EAST-LDL is a prospective, multicenter, randomized, open-label clinical trial with blinded endpoint assessment evaluating whether early intensive lipid lowering with the PCSK9 inhibitor recaticimab, administered before endovascular therapy, improves functional outcome in patients with acute ischemic stroke due to anterior-circulation large-vessel occlusion. Participants are randomized to recaticimab plus guideline-recommended standard of care or standard of care alone. The primary outcome is favorable functional outcome, defined as a modified Rankin Scale score of 0-2 at 90 ± 7 days.
Detailed description
EAST-LDL is an investigator-initiated, prospective, multicenter, randomized, open-label clinical trial with blinded endpoint assessment conducted at approximately 20 stroke centers in China. Adults with acute ischemic stroke due to anterior-circulation large-vessel occlusion who are planned to undergo endovascular therapy within 24 hours of symptom onset or last known well are randomized 1:1 to the PCSK9 inhibitor group or the control group. Participants assigned to the PCSK9 inhibitor group receive guideline-recommended standard of care plus recaticimab 450 mg administered subcutaneously after randomization and before the first thrombectomy pass, whereas participants assigned to the control group receive guideline-recommended standard of care alone. The original target sample size was 652 participants. The protocol prespecified one sample-size re-estimation after approximately 50% of the initially planned participants had completed the 90-day primary outcome assessment. Following the prespecified re-estimation, the independent Data and Safety Monitoring Board recommended at its third meeting on August 3, 2026 that the total sample size be increased by 50%, from 652 to 978 participants, in accordance with the predefined adaptive rules. No unblinded treatment results were disclosed to the investigators or other members of the blinded study team. The current target sample size is therefore 978 participants. The primary outcome is favorable functional outcome at 90 ± 7 days, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary efficacy outcomes include the ordinal distribution of mRS scores, National Institutes of Health Stroke Scale (NIHSS) score and change from baseline, low-density lipoprotein cholesterol (LDL-C) goal attainment and change from baseline, changes in inflammatory markers, severe disability, all-cause mortality, recurrent ischemic stroke, new hemorrhagic stroke, major adverse cardiovascular events, and health-related quality of life assessed using the EuroQol 5-Dimension questionnaire. Safety outcomes include symptomatic intracranial hemorrhagic transformation, serious adverse events, and adverse events of special interest. The 90-day mRS outcome is assessed centrally by an independent Outcome Assessment Committee blinded to treatment allocation.
Interventions
DRUGguideline-recommended SoC
Guideline-recommended SoC, including but not limited to oral lipid-lowering drugs, antiplatelet aggregation drugs, anticoagulant drugs, antihypertensive drugs, etc. It is to be determined by the investigator based on the subject's treatment needs.
DRUGRecaticimab (intensive)
450 mg as three 150-mg subcutaneous injections after randomization and before the first thrombectomy pass. No additional PCSK9 inhibitor treatment is planned during the 90-day follow-up.
Sponsors
Shanghai East Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The trial is open-label to participants and treating investigators. Trained follow-up personnel and members of the central Outcome Assessment Committee are unaware of treatment allocation. The 90-day mRS is assessed centrally by blinded assessors using recorded follow-up interviews; disagreements between two assessors are adjudicated by a third blinded assessor.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (age 18 years and older); * Imaging diagnosis of acute ischemic stroke with anterior circulation large vessel occlusion (including: internal carotid artery, middle cerebral artery M1 and M2, anterior cerebral artery A1 and A2); * Planned to undergo endovascular intervention within 24 hours of symptom onset (or last known well time) according to local guidelines; * Provision of informed consent by the patient or his/her legally authorized representative (or by an appropriate agent according to local requirements).
Exclusion criteria
* ASPECTS score ≤5 on cranial CT imaging; * Pre-existing functional impairment, with mRS score \>2; * Patients who are allergic to PCSK9 inhibitors; * Patients who have received PCSK9 monoclonal antibody within 1 month prior to enrollment or PCSK9 siRNA therapy within 6 months prior to enrollment; * Severe renal insufficiency, defined as estimated glomerular filtration rate (eGFR) \< 15 mL/min/1.73m2 at final screening; * Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the upper limit of normal; * Severe, concomitant non-cardiovascular disease expected to reduce life expectancy to less than 3 months; * Pregnant or lactating women; * Patients who are participating in other clinical trials; * Other conditions deemed unsuitable for inclusion in the clinical study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| favorable functional outcome (defined as an mRS score of 0-2) | 90 ± 7 days | the rate (%) of good functional outcome at 90 days (modified Rankin Scale \[mRS\] score 0-2). Modified Rankin Scale scores of 0 or 1 indicate good function without or with symptoms but not disability, score of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mRS ordinal score | 90 ± 7 days | Modified Rankin Scale scores of 0 or 1 indicate good function without or with symptoms but not disability, score of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death. |
| Change from baseline in NIHSS score | Day 14±3 days or before discharge | 0-42, higher scores indicates worse severity |
| Change from baseline in LDL-C | Day 14±3 days or before discharge | Change from baseline in LDL-C at 14±3 days or before discharge |
| Change in inflammatory markers | Day 0, Day 14±3 days or before discharge | Change from baseline in inflammatory markers at 14±3 days or before discharge; |
| Rate of severe disability(defined as mRS score of 3-5) | 90 ± 7 days | Modified Rankin Scale scores of 0 or 1 indicate good function without or with symptoms but not disability, score of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death. |
| Incidence of recurrent ischemic stroke events | From randomization through Day 90 | Incidence of recurrent ischemic stroke events |
| Incidence of symptomatic intracranial hemorrhage transformation | Within 24-48 hours | Incidence of symptomatic intracranial hemorrhage transformation within 24-48h; |
| Incidence of patients with new hemorrhagic stroke | From randomization through Day 90 | Incidence of patients with new hemorrhagic stroke |
| Incidence of patients with major adverse cardiovascular events | From randomization through Day 90 | Incidence of major adverse cardiovascular events (MACEs) within 90 days |
| Number of patients with serious adverse events | From enrollment to 90 days | total number of serious adverse events reported during follow-up, according to standard definitions |
| Health related quality of life | 90 ± 7 days | according to the EQ-5D |
| NIHSS score | at 14±3 days or before discharge | 0-42, higher scores indicates worse severity |
| LDL-C goal attainment rate | at 14±3 days or before discharge | LDL-C attained equal or lower than 1.8mmol/L (70 mg/dL) |
| Mortality rate | 90 ± 7 days | Death within 90 days. |
Countries
China
Contacts
CONTACTGang Li, MD
STUDY_CHAIRShanghai East Hospital
Tongji University
Outcome results
None listed